Stereotactic Radiosurgery with Mouse Phantom Quality Assurance Using the Sarrp in a Murine Melanoma Brain Metastases Model

Abstract

To establish a novel preclinical model for stereotactic radiosurgery with combined mouse phantom quality assurance in the setting of murine melanoma brain metastases. All protocols were approved by our institutional IACUC. C57B6 mice underwent intracranial stereotactic injection of B16-F10 melanoma cells. 300 cells per 1 microliter suspension in PBS was injected 2 mm lateral and 1.5 mm anterior to the bregma. The needle was inserted to a depth of 2.5 mm from the surface of the brain. T1-post contrast MRI with gadolinium was performed on day 11 post injection using a 9.4 Tesla MRI (Bruker). DICOM images for MRI based planning were fused with cone beam computed tomography (CBCT) simulation performed on the same mice using the SARRP (Xstrahl). Anatomical match was completed for the MRI to CBCT fusion and gross tumor volume (GTV) was contoured. A single sagittal arc using a 3 mm collimator was used to plan a 60 degree arc encompassing the GTV. 18 Gy was prescribed to a point dose. Radiation was delivered on the same day and repeat MRI was performed 7 days after radiation treatment on day 18. Radiation dose delivered to the mouse was confirmed using two mouse phantoms previously published by Welch et al. One mouse phantom is in the axial orientation and one phantom is in the sagittal orientation. A representative planning MRI scan from Day 10 was fused to the CBCT obtained from the two mouse phantoms and radiochromic film was placed in the region of the presumed GTV. Optical density of the film was analyzed using film analysis based on our institutional ion chamber measurement and H-D curve. MRI images were analyzed with 3D slicer for tumor volumes. Statistics used include T-test for volume comparison and Kaplan Meier curve for survival. The experiment was designed with two arms. Mouse injected with melanoma cells without radiation treatment (no SRS) and mouse injected with melanoma cells treated with stereotactic radiosurgery of 18 Gy in 1 fraction (SRS). The average tumor volume at Day 11 was 2.48±1.37 mm3 in the no SRS arm versus 3.75±1.19 mm3 in the SRS arm (NS). In the SRS arm, GTV Dose max (Dmax), mean dose, and D95 was 2048±207 cGy, 1785±14 cGy, and 1722±12 cGy respectively. Using the axial and saggital phantom mice, the radiochromic film showed close precision as compared to projected isodose lines. Radiochromic film analysis showed a Dmax of 1903.4 cGy and 1972.7 cGy in the axial and saggital phantom mice respectively. Tumor volume 7 days after SRS showed 7.34±8.24 mm3 in the SRS arm and 60.20±40.4 mm3in the no SRS arm (p=0.009). All mice with no SRS died. Median overall survival (mOS) of no SRS group was 19 days. mOS was not reached in the SRS group with one death noted. Single fraction SRS of 18 Gy using a single arc can be delivered accurately with MRI T1-post contrast based treatment planning. Phantom mice allows for verification of dose delivery and accuracy.